VITamin D and OmegA-3 TriaL (VITAL): Interrelationship of Vitamin D and Vitamin K on Bone

维生素 D 和 OmegA-3 TriaL (VITAL)：维生素 D 和维生素 K 对骨骼的相互关系

• 批准号: 10453573
• 负责人: MERYL Susan LEBOFF
• 金额: $ 55.33万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453573
• 关键词: Affect; African American population; American; Ancillary Study; Architecture; Attenuated; Biological Markers; Blood specimen; Body mass index; Bone Density; Bone Diseases; Bone Matrix; Bone structure; Calcium; Cardiovascular Diseases; Cholecalciferol; Collection; Creatinine; Deposition; Deterioration; Dose; Dual-Energy X-Ray Absorptiometry; Elderly; Ethnic Origin; Fasting; Femoral Fractures; Fish Oils; Fracture; Goals; Grant; Guidelines; High Prevalence; Hip Fractures; Intake; Intestines; Kidney; Kidney Calculi; Knowledge; Malignant Neoplasms; Measures; Medical Records; Nephrolithiasis; Norway; Observational Study; Omega-3 Fatty Acids; Osteocalcin; Osteoporosis; Outcome; PTH gene; Parents; Participant; Peripheral; Placebos; Play; Primary Cancer Prevention; Production; Proteins; Public Health; Questionnaires; Race; Randomized; Randomized Controlled Trials; Recommendation; Resources; Risk; Risk Factors; Rodent Model; Role; Serum; Spottings; Structure; Supplementation; Testing; Tissues; Toxic effect; Trabecular Bone Score; United States National Institutes of Health; Urine; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Vitamin K; Vitamin K 1; Woman; X-Ray Computed Tomography; adjudicate; adjudication; age group; aged; bone; bone health; bone loss; bone mass; bone turnover; calcification; calcium absorption; calcium excretion; carboxylate; carboxylation; clinical care; cohort; cost; cost efficient; design; dietary; follow-up; fracture risk; fragility fracture; high risk; imaging study; improved; innovation; insight; matrix Gla protein; men; older men; older women; protein K; protein function; radiological imaging; recruit; sex; soft tissue; systematic review

ABSTRACT Osteoporosis is the most common bone disease; 53.6 million Americans have a reduced bone mass, which increases their risk of fragility fractures. In addition to the high prevalence of vitamin D deficiency, recent studies show that approximately 60% of older men and 40% of older women have inadequate vitamin K intakes. Growing evidence indicates that there are important interrelationships between vitamin D and vitamin K on bone. Vitamin D increases intestinal calcium absorption and stimulates production of two proteins, osteocalcin and matrix Gla protein. Vitamin K plays an essential role in activating these proteins so that osteocalcin incorporates calcium in bone and matrix Gla protein inhibits calcification in soft tissues, including the kidney. Both vitamins D and K are important for optimal function of these proteins. Although vitamin D supplements are widely used to improve bone health, trials of supplemental vitamin D alone in reducing fractures showed inconsistent results. Emerging evidence indicates that supplemental D in the context of low vitamin K status is less effective on bone health measures. Therefore, low vitamin K status may account for some of the inconsistencies of trials testing vitamin D and bone health and may contribute to toxicities attributed to high-dose vitamin D such as kidney stones. No previous randomized controlled trials have been adequately powered to test effects of vitamin K status on fracture risk or the interaction of vitamin K status with high-dose, supplemental vitamin D on bone. To fill knowledge gaps, we propose an innovative, ancillary study to the large, NIH-sponsored, VITamin D and OmegA-3 TriaL (VITAL). VITAL is testing effects of supplemental vitamin D3 (cholecalciferol, 2000 IU/d), and/or omega-3 fatty acids (fish oil, 1 g/d) in the primary prevention of cancer and cardiovascular disease in 25,871 U.S. men (aged ≥50) and women (aged ≥55), including 5,106 African Americans. In this competitive renewal application of “VITAL: Effects on Bone Structure and Architecture,” we will determine whether low vitamin K status, assessed by 3 sensitive biomarkers, modifies effects of supplemental vitamin D on fractures, bone mineral density (BMD) and structure, and secondarily on increases in urine calcium excretion, a risk factor for low BMD and kidney stones. During the first cycle of this grant, we surpassed recruitment goals and collected baseline and 2-yr post-randomization imaging studies for bone density, structure and architecture that will be used in the proposed studies (n=771). In addition, other key VITAL resources will be leveraged including: 16,953 baseline and 6,000 follow-up blood samples; measures of vitamin D, calcium, creatinine and parathyroid hormone; and adjudicated fractures and kidney stones. This proposal provides a unique opportunity to clarify in the largest study of supplemental vitamin D, the interdependencies of vitamins D and K and their roles on fractures, bone health measures, and urine calcium excretion. Findings from the proposed ancillary study will be critical to the interpretation of on-going vitamin D trials and provide new insights to advance clinical care and public health recommendations.

摘要

项目成果

Update on the Vitamin D and OmegA-3 trial (VITAL).

• DOI: 10.1016/j.jsbmb.2015.04.006
• 发表时间: 2016-01
• 期刊: The Journal of steroid biochemistry and molecular biology
• 作者: Pradhan AD;Manson JE
• 通讯作者: Manson JE

Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.

• DOI: 10.1007/s00198-015-3386-5
• 发表时间: 2016-01
• 期刊: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
• 作者: Weaver CM;Alexander DD;Boushey CJ;Dawson-Hughes B;Lappe JM;LeBoff MS;Liu S;Looker AC;Wallace TC;Wang DD
• 通讯作者: Wang DD

Osteoanabolic Agents for Osteoporosis.

• DOI: 10.1210/js.2018-00118
• 发表时间: 2018-08-01
• 期刊: Journal of the Endocrine Society
• 影响因子: 4.1
• 作者: Haas AV;LeBoff MS
• 通讯作者: LeBoff MS

Low vitamin D status in Europe: moving from evidence to sound public health policies.

欧洲维生素 D 水平较低：从证据转向健全的公共卫生政策。

• DOI: 10.3945/ajcn.116.132274
• 发表时间: 2016
• 期刊: The American journal of clinical nutrition
• 作者: Quraishi,SadeqA;CamargoJr,CarlosA;Manson,JoAnnE
• 通讯作者: Manson,JoAnnE

Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials.

• DOI: 10.1093/nutrit/nuv012
• 发表时间: 2015-09
• 期刊: Nutrition reviews
• 影响因子: 6.1
• 作者: Chandler PD;Wang L;Zhang X;Sesso HD;Moorthy MV;Obi O;Lewis J;Prince RL;Danik JS;Manson JE;LeBoff MS;Song Y
• 通讯作者: Song Y